DESCRIPTION

The chemical name of empagliflozin is
D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-,
(1S).

Its molecular formula is C23H27ClO7
and the molecular weight is 450.91. The structural formula is:

Empagliflozin is a white to yellowish, non-hygroscopic
powder. It is very slightly soluble in water, sparingly soluble in methanol,
slightly soluble in ethanol and acetonitrile; soluble in 50%
acetonitrile/water; and practically insoluble in toluene.

Clinical Trials Experience

Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in practice.

Pool Of Placebo-Controlled Trials Evaluating JARDIANCE 10
And 25 mg

The data in Table 1 are derived from a pool of four
24-week placebo-controlled trials and 18-week data from a placebo-controlled
trial with insulin. JARDIANCE was used as monotherapy in one trial and as
add-on therapy in four trials [see Clinical Studies].

These data reflect exposure of 1976 patients to JARDIANCE
with a mean exposure duration of approximately 23 weeks. Patients received
placebo (N=995), JARDIANCE 10 mg (N=999), or JARDIANCE 25 mg (N=977) once
daily. The mean age of the population was 56 years and 3% were older than 75
years of age. More than half (55%) of the population was male; 46% were White, 50%
were Asian, and 3% were Black or African American. At baseline, 57% of the
population had diabetes more than 5 years and had a mean hemoglobin A1c (HbA1c)
of 8%. Established microvascular complications of diabetes at baseline included
diabetic nephropathy (7%), retinopathy (8%), or neuropathy (16%). Baseline
renal function was normal or mildly impaired in 91% of patients and moderately
impaired in 9% of patients (mean eGFR 86.8 mL/min/1.73 m2).

Table 1 shows common adverse reactions (excluding
hypoglycemia) associated with the use of JARDIANCE. The adverse reactions were
not present at baseline, occurred more commonly on JARDIANCE than on placebo and
occurred in greater than or equal to 2% of patients treated with JARDIANCE 10
mg or JARDIANCE 25 mg.

Volume Depletion

JARDIANCE causes an osmotic diuresis, which may lead to
intravascular volume contraction and adverse reactions related to volume
depletion. In the pool of five placebo-controlled clinical trials, adverse
reactions related to volume depletion (e.g., blood pressure (ambulatory)
decreased, blood pressure systolic decreased, dehydration, hypotension,
hypovolemia, orthostatic hypotension, and syncope) were reported by 0.3%, 0.5%,
and 0.3% of patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg
respectively. JARDIANCE may increase the risk of hypotension in patients at
risk for volume contraction [see WARNINGS AND PRECAUTIONS and Use in
Specific Populations].

Increased Urination

In the pool of five placebo-controlled clinical trials,
adverse reactions of increased urination (e.g., polyuria, pollakiuria, and
nocturia) occurred more frequently on JARDIANCE than on placebo (see Table 1). Specifically,
nocturia was reported by 0.4%, 0.3%, and 0.8% of patients treated with placebo,
JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.

Acute Impairment In Renal Function

Treatment with JARDIANCE was associated with increases in
serum creatinine and decreases in eGFR (see Table 2). Patients with moderate
renal impairment at baseline had larger mean changes [see WARNINGS AND
PRECAUTIONS and Use in Specific Populations].

In a long-term cardiovascular outcome trial, the acute
impairment in renal function was observed to reverse after treatment
discontinuation suggesting acute hemodynamic changes play a role in the renal
function changes observed with empagliflozin.

Table 2 : Changes from Baseline in Serum Creatinine
and eGFRa in the Pool of Four 24-week Placebo-Controlled Studies and
Renal Impairment Study

Pool of 24-Week Placebo-Controlled Studies

Placebo

JARDIANCE 10 mg

JARDIANCE 25 mg

Baseline Mean

N

825

830

822

Creatinine (mg/dL)

0.84

0.85

0.85

eGFR (mL/min/1.73 m²)

87.3

87.1

87.8

Week 12 Change

N

771

797

783

Creatinine (mg/dL)

0.00

0.02

0.01

eGFR (mL/min/1.73 m²)

-0.3

-1.3

-1.4

Week 24 Change

N

708

769

754

Creatinine (mg/dL)

0.00

0.01

0.01

eGFR (mL/min/1.73 m2)

-0.3

-0.6

-1.4

Moderate Renal Impairmentb

Placebo

JARDIANCE 25 mg

Baseline Mean

N

187

--

187

Creatinine (mg/dL)

1.49

--

1.46

eGFR (mL/min/1.73 m²)

44.3

--

45.4

Week 12 Change

N

176

--

179

Creatinine (mg/dL)

0.01

--

0.12

eGFR (mL/min/1.73 m²)

0.1

--

-3.8

Week 24 Change

N

170

--

171

Creatinine (mg/dL)

0.01

--

0.10

eGFR (mL/min/1.73 m²)

0.2

--

-3.2

Week 52 Change

N

164

--

162

Creatinine (mg/dL)

0.02

--

0.11

eGFR (mL/min/1.73 m²)

-0.3

--

-2.8

Post-treatment Changec

N

98

--

103

Creatinine (mg/dL)

0.03

--

0.02

eGFR (mL/min/1.73 m²)

0.16

--

1.48

aObserved cases on treatment.bSubset of patients from renal impairment study with eGFR 30 to less
than 60 mL/min/1.73 m2cApproximately 3 weeks after end of treatment.

The incidence of hypoglycemia by study is shown in Table
3. The incidence of hypoglycemia increased when JARDIANCE was administered with
insulin or sulfonylurea [see WARNINGS AND PRECAUTIONS].

aOverall hypoglycemic events: plasma or
capillary glucose of less than or equal to 70 mg/DlbSevere hypoglycemic events: requiring assistance regardless of
blood glucosecTreated set (patients who had received at least one dose of study
drug)dInsulin dose could not be adjusted during the initial 18 week
treatment period

Genital Mycotic Infections

In the pool of five placebo-controlled clinical trials,
the incidence of genital mycotic infections (e.g., vaginal mycotic infection,
vaginal infection, genital infection fungal, vulvovaginal candidiasis, and
vulvitis) was increased in patients treated with JARDIANCE compared to placebo,
occurring in 0.9%, 4.1%, and 3.7% of patients randomized to placebo, JARDIANCE
10 mg, and JARDIANCE 25 mg, respectively. Discontinuation from study due to
genital infection occurred in 0% of placebo-treated patients and 0.2% of
patients treated with either JARDIANCE 10 or 25 mg.

Urinary Tract Infections

In the pool of five placebo-controlled clinical trials,
the incidence of urinary tract infections (e.g., urinary tract infection,
asymptomatic bacteriuria, and cystitis) was increased in patients treated with
JARDIANCE compared to placebo (see Table 1). Patients with a history of chronic
or recurrent urinary tract infections were more likely to experience a urinary
tract infection. The rate of treatment discontinuation due to urinary tract
infections was 0.1%, 0.2%, and 0.1% for placebo, JARDIANCE 10 mg, and JARDIANCE
25 mg, respectively.

Increase in Hematocrit

In a pool of four placebo-controlled studies, median
hematocrit decreased by 1.3% in placebo and increased by 2.8% in JARDIANCE 10
mg and 2.8% in JARDIANCE 25 mg treated patients. At the end of treatment, 0.6%,
2.7%, and 3.5% of patients with hematocrits initially within the reference
range had values above the upper limit of the reference range with placebo,
JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.

Postmarketing Experience

Additional adverse reactions have been identified during
postapproval use of JARDIANCE. Because these reactions are reported voluntarily
from a population of uncertain size, it is generally not possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.

DRUG INTERACTIONS

Diuretics

Coadministration of empagliflozin with diuretics resulted
in increased urine volume and frequency of voids, which might enhance the
potential for volume depletion [see WARNINGS AND PRECAUTIONS].

Insulin Or Insulin Secretagogues

Coadministration of empagliflozin with insulin or insulin
secretagogues increases the risk for hypoglycemia [see WARNINGS AND
PRECAUTIONS].

Positive Urine Glucose Test

Monitoring glycemic control with urine glucose tests is
not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors
increase urinary glucose excretion and will lead to positive urine glucose
tests. Use alternative methods to monitor glycemic control.

Interference With 1,5-anhydroglucitol (1,5-AG) Assay

Monitoring glycemic control with 1,5-AG assay is not
recommended as measurements of 1,5-AG are unreliable in assessing glycemic
control in patients taking SGLT2 inhibitors. Use alternative methods to monitor
glycemic control.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypotension

JARDIANCE causes intravascular volume contraction.
Symptomatic hypotension may occur after initiating JARDIANCE [seeADVERSE
REACTIONS] particularly in patients with renal impairment, the elderly, in patients
with low systolic blood pressure, and in patients on diuretics. Before
initiating JARDIANCE, assess for volume contraction and correct volume status
if indicated. Monitor for signs and symptoms of hypotension after initiating
therapy and increase monitoring in clinical situations where volume contraction
is expected [see Use in Specific Populations].

Ketoacidosis

Reports of ketoacidosis, a serious life-threatening
condition requiring urgent hospitalization have been identified in
postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus
receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including
JARDIANCE. Fatal cases of ketoacidosis have been reported in patients taking
JARDIANCE. JARDIANCE is not indicated for the treatment of patients with type 1
diabetes mellitus [seeINDICATIONS AND USAGE].

Patients treated with JARDIANCE who present with signs
and symptoms consistent with severe metabolic acidosis should be assessed for
ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated
with JARDIANCE may be present even if blood glucose levels are less than 250
mg/dL. If ketoacidosis is suspected, JARDIANCE should be discontinued, patient
should be evaluated, and prompt treatment should be instituted. Treatment of
ketoacidosis may require insulin, fluid and carbohydrate replacement.

In many of the postmarketing reports, and particularly in
patients with type 1 diabetes, the presence of ketoacidosis was not immediately
recognized and institution of treatment was delayed because presenting blood glucose
levels were below those typically expected for diabetic ketoacidosis (often
less than 250 mg/dL). Signs and symptoms at presentation were consistent with
dehydration and severe metabolic acidosis and included nausea, vomiting,
abdominal pain, generalized malaise, and shortness of breath. In some but not
all cases, factors predisposing to ketoacidosis such as insulin dose reduction,
acute febrile illness, reduced caloric intake due to illness or surgery,
pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes,
history of pancreatitis or pancreatic surgery), and alcohol abuse were identified.

Before initiating JARDIANCE, consider factors in the
patient history that may predispose to ketoacidosis including pancreatic
insulin deficiency from any cause, caloric restriction, and alcohol abuse. In
patients treated with JARDIANCE consider monitoring for ketoacidosis and
temporarily discontinuing JARDIANCE in clinical situations known to predispose
to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).

Acute Kidney Injury And Impairment In Renal Function

JARDIANCE causes intravascular volume contraction [see
Hypotension] and can cause renal impairment [seeADVERSE
REACTIONS]. There have been postmarketing reports of acute kidney injury, some
requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors,
including JARDIANCE; some reports involved patients younger than 65 years of
age.

JARDIANCE increases serum creatinine and decreases eGFR.
Patients with hypovolemia may be more susceptible to these changes. Renal
function abnormalities can occur after initiating JARDIANCE [seeADVERSE
REACTIONS]. Renal function should be evaluated prior to initiation of
JARDIANCE and monitored periodically thereafter. More frequent renal function
monitoring is recommended in patients with an eGFR below 60 mL/min/1.73 m2. Use
of JARDIANCE is not recommended when eGFR is persistently less than 45 mL/min/1.73
m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 [seeDOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, Use in
Specific Populations].

Urosepsis And Pyelonephritis

There have been postmarketing reports of serious urinary
tract infections including urosepsis and pyelonephritis requiring
hospitalization in patients receiving SGLT2 inhibitors, including JARDIANCE.
Treatment with SGLT2 inhibitors increases the risk for urinary tract
infections. Evaluate patients for signs and symptoms of urinary tract
infections and treat promptly, if indicated [see ADVERSE REACTIONS].

Hypoglycemia With Concomitant Use With Insulin And
Insulin Secretagogues

Insulin and insulin secretagogues are known to cause
hypoglycemia. The risk of hypoglycemia is increased when JARDIANCE is used in
combination with insulin secretagogues (e.g., sulfonylurea) or insulin [seeADVERSE REACTIONS]. Therefore, a lower dose of the insulin secretagogue or
insulin may be required to reduce the risk of hypoglycemia when used in
combination with JARDIANCE.

Genital Mycotic Infections

JARDIANCE increases the risk for genital mycotic
infections [seeADVERSE REACTIONS]. Patients with a history of chronic
or recurrent genital mycotic infections were more likely to develop mycotic
genital infections. Monitor and treat as appropriate.

Increased Low-Density Lipoprotein Cholesterol (LDL-C)

Increases in LDL-C can occur with JARDIANCE [seeADVERSE REACTIONS]. Monitor and treat as appropriate.

Patient Counseling Information

Instructions

Instruct patients to read the PATIENT INFORMATION before
starting JARDIANCE therapy and to reread it each time the prescription is
renewed. Instruct patients to inform their doctor or pharmacist if they develop
any unusual symptom, or if any known symptom persists or worsens.

Inform patients of the potential risks and benefits of
JARDIANCE and of alternative modes of therapy. Also inform patients about the
importance of adherence to dietary instructions, regular physical activity,
periodic blood glucose monitoring and HbA1c testing, recognition and management
of hypoglycemia and hyperglycemia, and assessment for diabetes complications.
Advise patients to seek medical advice promptly during periods of stress such
as fever, trauma, infection, or surgery, as medication requirements may change.

Instruct patients to take JARDIANCE only as prescribed.
If a dose is missed, it should be taken as soon as the patient remembers.
Advise patients not to double their next dose.

Inform patients that the most common adverse reactions
associated with the use of JARDIANCE are urinary tract infections and mycotic
genital infections.

Inform female patients of reproductive potential that the
use of JARDIANCE during pregnancy has not been studied in humans, and that
JARDIANCE should only be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus. Based on animal data, JARDIANCE may cause
fetal harm in the second and third trimesters. Instruct patients to report
pregnancies to their physicians as soon as possible.

Inform nursing mothers to discontinue JARDIANCE or
nursing, taking into account the importance of the drug to the mother. It is
not known if JARDIANCE is excreted in breast milk; however, based on animal
data, JARDIANCE may cause harm to nursing infants.

Hypotension

Inform patients that hypotension may occur with JARDIANCE
and advise them to contact their healthcare provider if they experience such
symptoms [see WARNINGS AND PRECAUTIONS]. Inform patients that dehydration
may increase the risk for hypotension, and to have adequate fluid intake.

Ketoacidosis

Inform patients that ketoacidosis is a serious
life-threatening condition. Cases of ketoacidosis have been reported during use
of JARDIANCE. Instruct patients to check keto+nes (when possible) if symptoms
consistent with ketoacidosis occur even if blood glucose is not elevated. If
symptoms of ketoacidosis (including nausea, vomiting, abdominal pain,
tiredness, and labored breathing) occur, instruct patients to discontinue
JARDIANCE and seek medical advice immediately [see WARNINGS AND PRECAUTIONS].

Acute Kidney Injury

Inform patients that acute kidney injury has been
reported during use of JARDIANCE. Advise patients to seek medical advice
immediately if they have reduced oral intake (such as due to acute illness or
fasting) or increased fluid losses (such as due to vomiting, diarrhea, or
excessive heat exposure), as it may be appropriate to temporarily discontinue
JARDIANCE use in those settings [see WARNINGS AND PRECAUTIONS].

Serious Urinary Tract Infections

Inform patients of the potential for urinary tract
infections, which may be serious. Provide them with information on the symptoms
of urinary tract infections. Advise them to seek medical advice if such
symptoms occur [see WARNINGS AND PRECAUTIONS].

Genital Mycotic Infections In Females (e.g.,
Vulvovaginitis)

Inform female patients that vaginal yeast infections may
occur and provide them with information on the signs and symptoms of vaginal
yeast infections. Advise them of treatment options and when to seek medical
advice [see WARNINGS AND PRECAUTIONS].

Inform male patients that yeast infection of penis (e.g.,
balanitis or balanoposthitis) may occur, especially in uncircumcised males and
patients with chronic and recurrent infections. Provide them with information
on the signs and symptoms of balanitis and balanoposthitis (rash or redness of
the glans or foreskin of the penis). Advise them of treatment options and when
to seek medical advice [see WARNINGS AND PRECAUTIONS].

Laboratory Tests

Inform patients that renal function should be assessed
prior to initiation of JARDIANCE and monitored periodically thereafter.

Inform patients that elevated glucose in urinalysis is
expected when taking JARDIANCE.

Inform patients that response to all diabetic therapies
should be monitored by periodic measurements of blood glucose and HbA1c levels,
with a goal of decreasing these levels toward the normal range. Hemoglobin A1c monitoring
is especially useful for evaluating long-term glycemic control.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Carcinogenesis was evaluated in 2-year studies conducted
in CD-1 mice and Wistar rats. Empagliflozin did not increase the incidence of
tumors in female rats dosed at 100, 300, or 700 mg/kg/day (up to 72 times the exposure
from the maximum clinical dose of 25 mg). In male rats, hemangiomas of the
mesenteric lymph node were increased significantly at 700 mg/kg/day or
approximately 42 times the exposure from a 25 mg clinical dose. Empagliflozin
did not increase the incidence of tumors in female mice dosed at 100, 300, or
1000 mg/kg/day (up to 62 times the exposure from a 25 mg clinical dose). Renal
tubule adenomas and carcinomas were observed in male mice at 1000 mg/kg/day,
which is approximately 45 times the exposure of the maximum clinical dose of 25
mg. These tumors may be associated with a metabolic pathway predominantly
present in the male mouse kidney.

Mutagenesis

Empagliflozin was not mutagenic or clastogenic with or
without metabolic activation in the in vitro Ames bacterial mutagenicity assay,
the in vitro L5178Y tk+/- mouse lymphoma cell assay, and an in vivo micronucleus
assay in rats.

Impairment Of Fertility

Empagliflozin had no effects on mating, fertility or
early embryonic development in treated male or female rats up to the high dose
of 700 mg/kg/day (approximately 155 times the 25 mg clinical dose in males and
females, respectively).

Use In Specific Populations

Pregnancy

Risk Summary

Based on animal data showing adverse renal effects,
JARDIANCE is not recommended during the second and third trimesters of
pregnancy.

Limited data available with JARDIANCE in pregnant women
are not sufficient to determine a drug-associated risk for major birth defects
and miscarriage. There are risks to the mother and fetus associated with poorly
controlled diabetes in pregnancy [see Clinical Considerations].

In animal studies, adverse renal changes were observed in
rats when empagliflozin was administered during a period of renal development
corresponding to the late second and third trimesters of human pregnancy. Doses
approximately 13-times the maximum clinical dose caused renal pelvic and tubule
dilatations that were reversible. Empagliflozin was not teratogenic in rats and
rabbits up to 300 mg/kg/day, which approximates 48- times and 128-times,
respectively, the maximum clinical dose of 25 mg when administered during organogenesis
[see Data].

The estimated background risk of major birth defects is
6-10% in women with pre-gestational diabetes with a HbA1c > 7 and has been
reported to be as high as 20-25% in women with HbA1c > 10. The estimated background
risk of miscarriage for the indicated population is unknown. In the U.S.
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively.

Data

Animal Data

Empagliflozin dosed directly to juvenile rats from
postnatal day (PND) 21 until PND 90 at doses of 1, 10, 30 and 100 mg/kg/day
caused increased kidney weights and renal tubular and pelvic dilatation at 100
mg/kg/day, which approximates 13-times the maximum clinical dose of 25 mg,
based on AUC. These findings were not observed after a 13 week drug-free
recovery period. These outcomes occurred with drug exposure during periods of
renal development in rats that correspond to the late second and third
trimester of human renal development.

In embryo-fetal development studies in rats and rabbits,
empagliflozin was administered for intervals coinciding with the first
trimester period of organogenesis in humans. Doses up to 300 mg/kg/day, which
approximates 48- times (rats) and 128-times (rabbits) the maximum clinical dose
of 25 mg (based on AUC), did not result in adverse developmental effects. In
rats, at higher doses of empagliflozin causing maternal toxicity, malformations
of limb bones increased in fetuses at 700 mg/kg/day or 154-times the 25 mg
maximum clinical dose. In the rabbit, higher doses of empagliflozin resulted in
maternal and fetal toxicity at 700 mg/kg/day, or 139-times the 25 mg maximum
clinical dose.

In pre- and postnatal development studies in pregnant
rats, empagliflozin was administered from gestation day 6 through to lactation
day 20 (weaning) at up to 100 mg/kg/day (approximately 16 times the 25 mg
maximum clinical dose) without maternal toxicity. Reduced body weight was
observed in the offspring at greater than or equal to 30 mg/kg/day
(approximately 4 times the 25 mg maximum clinical dose).

Lactation

Risk Summary

There is no information regarding the presence of
JARDIANCE in human milk, the effects of JARDIANCE on the breastfed infant or
the effects on milk production. Empagliflozin is present in the milk of
lactating rats [see Data]. Since human kidney maturation occurs in utero
and during the first 2 years of life when lactational exposure may occur, there
may be risk to the developing human kidney.

Because of the potential for serious adverse reactions in
a breastfed infant, advise women that use of JARDIANCE is not recommended while
breastfeeding.

Data

Empagliflozin was present at a low level in rat fetal
tissues after a single oral dose to the dams at gestation day 18. In rat milk,
the mean milk to plasma ratio ranged from 0.634 -5, and was greater than one
from 2 to 24 hours post-dose. The mean maximal milk to plasma ratio of 5
occurred at 8 hours post-dose, suggesting accumulation of empagliflozin in the
milk. Juvenile rats directly exposed to empagliflozin showed a risk to the developing
kidney (renal pelvic and tubular dilatations) during maturation.

Pediatric Use

The safety and effectiveness of JARDIANCE in pediatric
patients under 18 years of age have not been established.

Geriatric Use

No JARDIANCE dosage change is recommended based on age [seeDOSAGE AND ADMINISTRATION]. In studies assessing the efficacy of empagliflozin
in improving glycemic control in patients with type 2 diabetes, a total of 2721
(32%) patients treated with empagliflozin were 65 years of age and older, and
491 (6%) were 75 years of age and older. JARDIANCE is expected to have
diminished glycemic efficacy in elderly patients with renal impairment [see
Use in Specific Populations]. The risk of volume depletion-related adverse reactions
increased in patients who were 75 years of age and older to 2.1%, 2.3%, and
4.4% for placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg. The risk of urinary
tract infections increased in patients who were 75 years of age and older to
10.5%, 15.7%, and 15.1% in patients randomized to placebo, JARDIANCE 10 mg, and
JARDIANCE 25 mg, respectively [see WARNINGS AND PRECAUTIONS and ADVERSE
REACTIONS].

Renal Impairment

The efficacy and safety of JARDIANCE were evaluated in a
study of patients with mild and moderate renal impairment [seeClinical
Studies]. In this study, 195 patients exposed to JARDIANCE had an eGFR between
60 and 90 mL/min/1.73 m2, 91 patients exposed to JARDIANCE had an eGFR between
45 and 60 mL/min/1.73 m2 and 97 patients exposed to JARDIANCE had an eGFR
between 30 and 45 mL/min/1.73 m2. The glucose lowering benefit of JARDIANCE 25
mg decreased in patients with worsening renal function. The risks of renal
impairment [see WARNINGS AND PRECAUTIONS], volume depletion adverse
reactions and urinary tract infection-related adverse reactions increased with
worsening renal function.

In a large cardiovascular outcomes study, there were 1819
patients with eGFR below 60 mL/min/1.73 m2. The cardiovascular death findings
in this subgroup were consistent with the overall findings [see Clinical
Studies].

The efficacy and safety of JARDIANCE have not been
established in patients with severe renal impairment, with ESRD, or receiving
dialysis. JARDIANCE is not expected to be effective in these patient
populations [seeDOSAGE AND ADMINISTRATION, CONTRAINDICATIONS and
WARNINGS AND PRECAUTIONS].

Hepatic Impairment

OVERDOSE

In the event of an overdose with JARDIANCE, contact the
Poison Control Center. Employ the usual supportive measures (e.g., remove
unabsorbed material from the gastrointestinal tract, employ clinical
monitoring, and institute supportive treatment) as dictated by the patient's
clinical status. Removal of empagliflozin by hemodialysis has not been studied.

CLINICAL PHARMACOLOGY

Mechanism Of Action

Sodium-glucose co-transporter 2 (SGLT2) is the
predominant transporter responsible for reabsorption of glucose from the
glomerular filtrate back into the circulation. Empagliflozin is an inhibitor of
SGLT2. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of
filtered glucose and lowers the renal threshold for glucose, and thereby
increases urinary glucose excretion.

Pharmacodynamics

Urinary Glucose Excretion

In patients with type 2 diabetes, urinary glucose
excretion increased immediately following a dose of JARDIANCE and was
maintained at the end of a 4-week treatment period averaging at approximately
64 grams per day with 10 mg empagliflozin and 78 grams per day with 25 mg
JARDIANCE once daily [see Clinical Studies].

Urinary Volume

In a 5-day study, mean 24-hour urine volume increase from
baseline was 341 mL on Day 1 and 135 mL on Day 5 of empagliflozin 25 mg once
daily treatment.

Cardiac Electrophysiology

In a randomized, placebo-controlled, active-comparator,
crossover study, 30 healthy subjects were administered a single oral dose of
JARDIANCE 25 mg, JARDIANCE 200 mg (8 times the maximum dose), moxifloxacin, and
placebo. No increase in QTc was observed with either 25 mg or 200 mg
empagliflozin.

Pharmacokinetics

Absorption

The pharmacokinetics of empagliflozin has been
characterized in healthy volunteers and patients with type 2 diabetes and no
clinically relevant differences were noted between the two populations. After
oral administration, peak plasma concentrations of empagliflozin were reached
at 1.5 hours post-dose. Thereafter, plasma concentrations declined in a
biphasic manner with a rapid distribution phase and a relatively slow terminal
phase. The steady state mean plasma AUC and Cmax were 1870 nmol•h/L and 259
nmol/L, respectively, with 10 mg empagliflozin once daily treatment, and 4740
nmol•h/L and 687 nmol/L, respectively, with 25 mg empagliflozin once daily
treatment. Systemic exposure of empagliflozin increased in a doseproportional manner
in the therapeutic dose range. The single-dose and steady-state pharmacokinetic
parameters of empagliflozin were similar, suggesting linear pharmacokinetics
with respect to time.

Administration of 25 mg empagliflozin after intake of a
high-fat and high-calorie meal resulted in slightly lower exposure; AUC
decreased by approximately 16% and Cmax decreased by approximately 37%,
compared to fasted condition. The observed effect of food on empagliflozin
pharmacokinetics was not considered clinically relevant and empagliflozin may
be administered with or without food.

Distribution

The apparent steady-state volume of distribution was
estimated to be 73.8 L based on a population pharmacokinetic analysis.
Following administration of an oral [14C]-empagliflozin solution to healthy
subjects, the red blood cell partitioning was approximately 36.8% and plasma
protein binding was 86.2%.

Metabolism

No major metabolites of empagliflozin were detected in
human plasma and the most abundant metabolites were three glucuronide
conjugates (2-O-, 3-O-, and 6-O-glucuronide). Systemic exposure of each
metabolite was less than 10% of total drug-related material. In vitro studies
suggested that the primary route of metabolism of empagliflozin in humans is
glucuronidation by the uridine 5'-diphospho-glucuronosyltransferases UGT2B7, UGT1A3,
UGT1A8, and UGT1A9.

Elimination

The apparent terminal elimination half-life of
empagliflozin was estimated to be 12.4 h and apparent oral clearance was 10.6
L/h based on the population pharmacokinetic analysis. Following once-daily
dosing, up to 22% accumulation, with respect to plasma AUC, was observed at
steady-state, which was consistent with empagliflozin half-life. Following
administration of an oral [14C]-empagliflozin solution to healthy subjects, approximately
95.6% of the drug-related radioactivity was eliminated in feces (41.2%) or
urine (54.4%). The majority of drug-related radioactivity recovered in feces
was unchanged parent drug and approximately half of drug-related radioactivity
excreted in urine was unchanged parent drug.

Specific Populations

Renal Impairment

In patients with mild (eGFR: 60 to less than 90
mL/min/1.73 m2), moderate (eGFR: 30 to less than 60 mL/min/1.73 m2), and severe
(eGFR: less than 30 mL/min/1.73 m2) renal impairment and subjects with kidney failure/end
stage renal disease (ESRD) patients, AUC of empagliflozin increased by
approximately 18%, 20%, 66%, and 48%, respectively, compared to subjects with
normal renal function. Peak plasma levels of empagliflozin were similar in
subjects with moderate renal impairment and kidney failure/ESRD compared to patients
with normal renal function. Peak plasma levels of empagliflozin were roughly
20% higher in subjects with mild and severe renal impairment as compared to
subjects with normal renal function. Population pharmacokinetic analysis showed
that the apparent oral clearance of empagliflozin decreased, with a decrease in
eGFR leading to an increase in drug exposure. However, the fraction of
empagliflozin that was excreted unchanged in urine, and urinary glucose
excretion, declined with decrease in eGFR.

Hepatic Impairment

In subjects with mild, moderate, and severe hepatic
impairment according to the Child-Pugh classification, AUC of empagliflozin
increased by approximately 23%, 47%, and 75%, and Cmax increased by
approximately 4%, 23%, and 48%, respectively, compared to subjects with normal
hepatic function.

Effects of Age, Body Mass Index, Gender, and Race

Based on the population PK analysis, age, body mass index
(BMI), gender and race (Asians versus primarily Whites) do not have a
clinically meaningful effect on pharmacokinetics of empagliflozin [seeUse
in Specific Populations].

Pediatric

Studies characterizing the pharmacokinetics of
empagliflozin in pediatric patients have not been performed.

Drug Interactions

In Vitro Assessment of Drug Interactions

Empagliflozin does not inhibit, inactivate, or induce
CYP450 isoforms. In vitro data suggest that the primary route of metabolism of
empagliflozin in humans is glucuronidation by the uridine
5'-diphosphoglucuronosyltransferases UGT1A3, UGT1A8, UGT1A9, and UGT2B7.
Empagliflozin does not inhibit UGT1A1, UGT1A3, UGT1A8, UGT1A9, or UGT2B7.
Therefore, no effect of empagliflozin is anticipated on concomitantly
administered drugs that are substrates of the major CYP450 isoforms or UGT1A1,
UGT1A3, UGT1A8, UGT1A9, or UGT2B7. The effect of UGT induction (e.g., induction
by rifampicin or any other UGT enzyme inducer) on empagliflozin exposure has
not been evaluated.

Empagliflozin is a substrate for P-glycoprotein (P-gp)
and breast cancer resistance protein (BCRP), but it does not inhibit these
efflux transporters at therapeutic doses. Based on in vitro studies,
empagliflozin is considered unlikely to cause interactions with drugs that are
P-gp substrates. Empagliflozin is a substrate of the human uptake transporters
OAT3, OATP1B1, and OATP1B3, but not OAT1 and OCT2. Empagliflozin does not inhibit
any of these human uptake transporters at clinically relevant plasma
concentrations and, therefore, no effect of empagliflozin is anticipated on
concomitantly administered drugs that are substrates of these uptake transporters.

In Vivo Assessment of Drug Interactions

No dose adjustment of JARDIANCE is recommended when
coadministered with commonly prescribed medicinal products based on results of
the described pharmacokinetic studies. Empagliflozin pharmacokinetics were
similar with and without coadministration of metformin, glimepiride,
pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, and
simvastatin in healthy volunteers and with or without coadministration of hydrochlorothiazide
and torsemide in patients with type 2 diabetes (see Figure 1). The observed
increases in overall exposure (AUC) of empagliflozin following coadministration
with gemfibrozil, rifampicin, or probenecid are not clinically relevant. In
subjects with normal renal function, coadministration of empagliflozin with
probenecid resulted in a 30% decrease in the fraction of empagliflozin excreted
in urine without any effect on 24-hour urinary glucose excretion. The relevance
of this observation to patients with renal impairment is unknown.

Clinical Studies

Glycemic Control

JARDIANCE has been studied as monotherapy and in
combination with metformin, sulfonylurea, pioglitazone, linagliptin, and
insulin. JARDIANCE has also been studied in patients with type 2 diabetes with
mild or moderate renal impairment.

In patients with type 2 diabetes, treatment with
JARDIANCE reduced hemoglobin A1c (HbA1c), compared to placebo. The reduction in
HbA1c for JARDIANCE compared with placebo was observed across subgroups including
gender, race, geographic region, baseline BMI and duration of disease.

Monotherapy

A total of 986 patients with type 2 diabetes participated
in a double-blind, placebo-controlled study to evaluate the efficacy and safety
of JARDIANCE monotherapy.

Treatment-na´ve patients with inadequately controlled
type 2 diabetes entered an open-label placebo run-in for 2 weeks. At the end of
the run-in period, patients who remained inadequately controlled and had an
HbA1c between 7 and 10% were randomized to placebo, JARDIANCE 10 mg, JARDIANCE
25 mg, or a reference comparator.

Figure 3 : Adjusted Mean HbA1c Change at Each Time
Point (Completers) and at Week 24 (mITT Population) - LOCF

At Week 24, the systolic blood pressure was statistically
significantly reduced compared to placebo by -2.6 mmHg (placebo-adjusted,
p-value=0.0231) in patients randomized to 10 mg of JARDIANCE and by -3.4 mmHg
(placebo-corrected, p-value=0.0028) in patients randomized to 25 mg of
JARDIANCE.

Add-On Combination Therapy With Metformin

A total of 637 patients with type 2 diabetes participated
in a double-blind, placebo-controlled study to evaluate the efficacy and safety
of JARDIANCE in combination with metformin.

Patients with type 2 diabetes inadequately controlled on
at least 1500 mg of metformin per day entered an openlabel 2 week placebo
run-in. At the end of the run-in period, patients who remained inadequately
controlled and had an HbA1c between 7 and 10% were randomized to placebo,
JARDIANCE 10 mg, or JARDIANCE 25 mg.

Initial Combination Therapy With Metformin

A total of 1364 patients with type 2 diabetes
participated in a double-blind, randomized, active-controlled study to evaluate
the efficacy and safety of JARDIANCE in combination with metformin as initial
therapy compared to the corresponding individual components.

Treatment-na´ve patients with inadequately controlled
type 2 diabetes entered an open-label placebo run-in for 2 weeks. At the end of
the run-in period, patients who remained inadequately controlled and had an
HbA1c between 7 and 10.5% were randomized to one of 8 active-treatment arms:
JARDIANCE 10 mg or 25 mg; metformin 1000 mg, or 2000 mg; JARDIANCE 10 mg in
combination with 1000 mg or 2000 mg metformin; or JARDIANCE 25 mg in
combination with 1000 mg or 2000 mg metformin.

Add-On Combination Therapy With Metformin And Sulfonylurea

A total of 666 patients with type 2 diabetes participated
in a double-blind, placebo-controlled study to evaluate the efficacy and safety
of JARDIANCE in combination with metformin plus a sulfonylurea.

Patients with inadequately controlled type 2 diabetes on
at least 1500 mg per day of metformin and on a sulfonylurea, entered a 2 week
open-label placebo run-in. At the end of the run-in, patients who remained inadequately
controlled and had an HbA1c between 7% and 10% were randomized to placebo,
JARDIANCE 10 mg, or JARDIANCE 25 mg.

In Combination With Linagliptin As Add-On To Metformin
Therapy

A total of 686 patients with type 2 diabetes participated
in a double-blind, active-controlled study to evaluate the efficacy and safety
of JARDIANCE 10 mg or 25 mg in combination with linagliptin 5 mg compared to
the individual components.

Patients with type 2 diabetes inadequately controlled on
at least 1500 mg of metformin per day entered a singleblind placebo run-in
period for 2 weeks. At the end of the run-in period, patients who remained
inadequately controlled and had an HbA1c between 7 and 10.5% were randomized
1:1:1:1:1 to one of 5 active-treatment arms of JARDIANCE 10 mg or 25 mg,
linagliptin 5 mg, or linagliptin 5 mg in combination with 10 mg or 25 mg
JARDIANCE as a fixed dose combination tablet.

The efficacy of JARDIANCE was evaluated in a double-blind,
glimepiride-controlled, study in 1545 patients with type 2 diabetes with
insufficient glycemic control despite metformin therapy.

Patients with inadequate glycemic control and an HbA1c
between 7% and 10% after a 2-week run-in period were randomized to glimepiride
or JARDIANCE 25 mg.

At Week 52, JARDIANCE 25 mg and glimepiride lowered HbA1c
and FPG (see Table 8, Figure 4). The difference in observed effect size between
JARDIANCE 25 mg and glimepiride excluded the pre-specified noninferiority margin
of 0.3%. The mean daily dose of glimepiride was 2.7 mg and the maximal approved
dose in the United States is 8 mg per day.

At Week 104, the adjusted mean change from baseline in
HbA1c was -0.75% for JARDIANCE 25 mg and -0.66% for glimepiride. The adjusted
mean treatment difference was -0.09% with a 97.5% confidence interval of
(-0.32%, 0.15%), excluding the pre-specified non-inferiority margin of 0.3%.
The mean daily dose of glimepiride was 2.7 mg and the maximal approved dose in
the United States is 8 mg per day. The Week 104 analysis included data with and
without concomitant glycemic rescue medication, as well as off-treatment data. Missing
data for patients not providing any information at the visit were imputed based
on the observed offtreatment data. In this multiple imputation analysis, 13.9%
of the data were imputed for JARDIANCE 25 mg and 12.9% for glimepiride.

Add-On Combination Therapy With Pioglitazone With Or
Without Metformin

A total of 498 patients with type 2 diabetes participated
in a double-blind, placebo-controlled study to evaluate the efficacy and safety
of JARDIANCE in combination with pioglitazone, with or without metformin.

Patients with inadequately controlled type 2 diabetes on
metformin at a dose of at least 1500 mg per day and pioglitazone at a dose of
at least 30 mg per day were placed into an open-label placebo run-in for 2
weeks. Patients with inadequate glycemic control and an HbA1c between 7% and
10% after the run-in period were randomized to placebo, JARDIANCE 10 mg, or
JARDIANCE 25 mg.

Add-On Combination With Insulin With Or Without Metformin
And/Or Sulfonylureas

A total of 494 patients with type 2 diabetes inadequately
controlled on insulin, or insulin in combination with oral drugs participated
in a double-blind, placebo-controlled study to evaluate the efficacy of
JARDIANCE as add-on therapy to insulin over 78 weeks.

Patients entered a 2-week placebo run-in period on basal
insulin (e.g., insulin glargine, insulin detemir, or NPH insulin) with or
without metformin and/or sulfonylurea background therapy. Following the run-in
period, patients with inadequate glycemic control were randomized to the
addition of JARDIANCE 10 mg, JARDIANCE 25 mg, or placebo. Patients were
maintained on a stable dose of insulin prior to enrollment, during the run-in
period, and during the first 18 weeks of treatment. For the remaining 60 weeks,
insulin could be adjusted. The mean total daily insulin dose at baseline for
JARDIANCE 10 mg, 25 mg, and placebo was 45 IU, 48 IU, and 48 IU, respectively.

Add-on Combination With MDI Insulin With Or Without Metformin

A total of 563 patients with type 2 diabetes inadequately
controlled on multiple daily injections (MDI) of insulin (total daily dose
> 60 IU), alone or in combination with metformin, participated in a
double-blind, placebo-controlled study to evaluate the efficacy of JARDIANCE as
add-on therapy to MDI insulin over 18 weeks.

Patients entered a 2-week placebo run-in period on MDI
insulin with or without metformin background therapy. Following the run-in
period, patients with inadequate glycemic control were randomized to the
addition of JARDIANCE 10 mg, JARDIANCE 25 mg, or placebo. Patients were maintained
on a stable dose of insulin prior to enrollment, during the run-in period, and
during the first 18 weeks of treatment. The mean total daily insulin dose at
baseline for JARDIANCE 10 mg, JARDIANCE 25 mg, and placebo was 88.6 IU, 90.4
IU, and 89.9 IU, respectively.

During an extension period with treatment for up to 52
weeks, insulin could be adjusted to achieve defined glucose target levels. The
change from baseline in HbA1c was maintained from 18 to 52 weeks with both JARDIANCE
10 mg and 25 mg. After 52 weeks, JARDIANCE 10 mg or 25 mg daily resulted in
statistically greater percent body weight reduction compared to placebo
(p-value < 0.0001). The mean change in body weight from baseline was -1.95 kg
for JARDIANCE 10 mg, and -2.04 kg for JARDIANCE 25 mg.

Renal Impairment

A total of 738 patients with type 2 diabetes and a
baseline eGFR less than 90 mL/min/1.73 m2 participated in a randomized,
double-blind, placebo-controlled, parallel-group to evaluate the efficacy and
safety of JARDIANCE in patients with type 2 diabetes and renal impairment. The
trial population comprised of 290 patients with mild renal impairment (eGFR 60
to less than 90 mL/min/1.73 m2), 374 patients with moderate renal impairment
(eGFR 30 to less than 60 mL/min/1.73 m2), and 74 with severe renal impairment (eGFR
less than 30 mL/min/1.73 m2). A total of 194 patients with moderate renal
impairment had a baseline eGFR of 30 to less than 45 mL/min/1.73 m2 and 180
patients a baseline eGFR of 45 to less than 60 mL/min/1.73 m2.

The glucose lowering efficacy of JARDIANCE 25 mg
decreased with decreasing level of renal function in the mild to moderate
range. Least square mean Hb1Ac changes at 24 weeks were -0.6%, -0.5%, and -0.2%
for those with a baseline eGFR of 60 to less than 90 mL/min/1.73 m2, 45 to less
than 60 mL/min/1.73 m2, and 30 to less than 45 mL/min/1.73 m2, respectively [see
DOSAGE AND ADMINISTRATION and Use in Specific Populations]. For
placebo, least square mean HbA1c changes at 24 weeks were 0.1%, -0.1%, and 0.2%
for patients with a baseline eGFR of 60 to less than 90 mL/min/1.73 m2, 45 to
less than 60 mL/min/1.73 m2, and 30 to less than 45 mL/min/1.73 m2,
respectively.

The effect of JARDIANCE on cardiovascular risk in adult
patients with type 2 diabetes and established, stable, atherosclerotic
cardiovascular disease was evaluated in the EMPA-REG OUTCOME study, a
multicenter, multi-national, randomized, double-blind parallel group trial. The
study compared the risk of experiencing a major adverse cardiovascular event
(MACE) between JARDIANCE and placebo when these were added to and used
concomitantly with standard of care treatments for diabetes and atherosclerotic
cardiovascular disease. Coadministered antidiabetic medications were to be kept
stable for the first 12 weeks of the trial. Thereafter, antidiabetic and
atherosclerotic therapies could be adjusted, at the discretion of
investigators, to ensure participants were treated according to the standard
care for these diseases.

A total of 7020 patients were treated (JARDIANCE 10 mg =
2345; JARDIANCE 25 mg = 2342; placebo = 2333) and followed for a median of 3.1
years. Approximately 72% of the study population was Caucasian, 22% was Asian,
and 5% was Black. The mean age was 63 years and approximately 72% were male.

All patients in the study had inadequately controlled
type 2 diabetes mellitus at baseline (HbA1c greater than or equal to 7%). The
mean HbA1c at baseline was 8.1% and 57% of participants had had diabetes for
more than 10 years. Approximately 31%, 22% and 20% reported a past history of
neuropathy, retinopathy and nephropathy to investigators respectively and the
mean eGFR was 74 mL/min/1.73 m2. At baseline, patients were treated with one
(~30%) or more (~70%) antidiabetic medications including metformin (74%),
insulin (48%), and sulfonylurea (43%).

All patients had established atherosclerotic
cardiovascular disease at baseline including one (82%) or more (18%) of the
following; a documented history of coronary artery disease (76%), stroke (23%)
or peripheral artery disease (21%). At baseline, the mean systolic blood
pressure was 136 mmHg, the mean diastolic blood pressure was 76 mmHg, the mean
LDL was 86 mg/dL, the mean HDL was 44 mg/dL, and the mean urinary albumin to
creatinine ratio (UACR) was 175 mg/g. At baseline, approximately 81% of
patients were treated with renin angiotensin system inhibitors, 65% with
beta-blockers, 43% with diuretics, 77% with statins, and 86% with antiplatelet
agents (mostly aspirin).

The primary endpoint in EMPA-REG OUTCOME was the time to
first occurrence of a Major Adverse Cardiac Event (MACE). A major adverse
cardiac event was defined as occurrence of either a cardiovascular death or a nonfatal
myocardial infarction (MI) or a nonfatal stroke. The statistical analysis plan
had pre-specified that the 10 and 25 mg doses would be combined. A Cox
proportional hazards model was used to test for non-inferiority against the
pre-specified risk margin of 1.3 for the hazard ratio of MACE and superiority
on MACE if noninferiority was demonstrated. Type-1 error was controlled across
multiples tests using a hierarchical testing strategy.

JARDIANCE significantly reduced the time to first
occurrence of primary composite endpoint of cardiovascular death, non-fatal myocardial
infarction, or non-fatal stroke (HR: 0.86; 95% CI 0.74, 0.99). The treatment
effect was due to a significant reduction in the risk of cardiovascular death
in subjects randomized to empagliflozin (HR: 0.62; 95% CI 0.49, 0.77), with no
change in the risk of non-fatal myocardial infarction or non-fatal stroke (see
Table 13 and Figure 5 and 6). Results for the 10 mg and 25 mg empagliflozin
doses were consistent with results for the combined dose groups.

Table 13 : Treatment Effect for the Primary Composite
Endpoint, and its Componentsa

aTreated set (patients who had received at
least one dose of study drug)bp-value for superiority (2-sided) 0.04cTotal number of events

Figure 5: Estimated Cumulative Incidence of First MACE

Figure 6 : Estimated Cumulative Incidence of
Cardiovascular Death

The efficacy of JARDIANCE on cardiovascular death was
generally consistent across major demographic and disease subgroups.

Vital status was obtained for 99.2% of subjects in the
trial. A total of 463 deaths were recorded during the EMPA-REG OUTCOME trial.
Most of these deaths were categorized as cardiovascular deaths. The
noncardiovascular deaths were only a small proportion of deaths, and were
balanced between the treatment groups (2.1% in patients treated with JARDIANCE,
and 2.4% of patients treated with placebo).

PATIENT INFORMATION

JARDIANCE®
(jar DEE ans)
(empagliflozin) Tablets

What is the most important information I should know
about JARDIANCE?

JARDIANCE can cause serious side effects, including:

Dehydration. JARDIANCE can cause some people to
have dehydration (the loss of body water and salt). Dehydration may cause you
to feel dizzy, faint, light-headed, or weak, especially when you stand up
(orthostatic hypotension).

Yeast infection of the penis (balanitis or
balanoposthitis). Men who take JARDIANCE may get a yeast infection of the
skin around the penis. Certain men who are not circumcised may have swelling of
the penis that makes it difficult to pull back the skin around the tip of the
penis. Other symptoms of yeast infection of the penis include:

redness, itching, or swelling of the penis

rash of the penis

foul smelling discharge from the penis

pain in the skin around penis

Talk to your doctor about what to do if you get symptoms
of a yeast infection of the vagina or penis. Your doctor may suggest you use an
over-the-counter antifungal medicine. Talk to your doctor right away if you use
an over-thecounter antifungal medication and your symptoms do not go away.

What is JARDIANCE?

JARDIANCE is a prescription medicine used:

along with diet and exercise to lower blood sugar in
adults with type 2 diabetes.

have or have had problems with your pancreas, including
pancreatitis or surgery on your pancreas

drink alcohol very often, or drink a lot of alcohol in
the short term ("binge" drinking)

have any other medical conditions

are pregnant or planning to become pregnant. It is not
known if JARDIANCE will harm your unborn baby. If you are pregnant, talk with
your doctor about the best way to control your blood sugar while you are
pregnant.

are breastfeeding or plan to breastfeed. It is not known
if JARDIANCE passes into your breast milk. Talk with your doctor about the best
way to feed your baby if you take JARDIANCE.

Tell your doctor about all the medicines you take,
including prescription and over-the-counter medicines, vitamins, and herbal
supplements.

JARDIANCE may affect the way other medicines work, and
other medicines may affect how JARDIANCE works.

Ask your doctor or pharmacist for a list of these
medicines if you are not sure if your medicine is listed above.

How should I take JARDIANCE?

Take JARDIANCE exactly as your doctor tells you to take
it.

Take JARDIANCE by mouth 1 time in the morning each day,
with or without food.

Your doctor may change your dose if needed.

If you miss a dose, take it as soon as you remember. If
you do not remember until it is time for your next dose, skip the missed dose
and go back to your regular schedule. Do not take two doses of JARDIANCE at the
same time. Talk with your doctor if you have questions about a missed dose.

Your doctor may tell you to take JARDIANCE along with
other diabetes medicines. Low blood sugar can happen more often when JARDIANCE is
taken with certain other diabetes medicines. See "What are the possible side
effects of JARDIANCE?"

If you take too much JARDIANCE, call your doctor or go to
the nearest hospital emergency room right away.

When your body is under some types of stress, such as
fever, trauma (such as a car accident), infection, or surgery, the amount of
diabetes medicine that you need may change. Tell your doctor right away if you
have any of these conditions and follow your doctor's instructions.

Check your blood sugar as your doctor tells you to.

Stay on your prescribed diet and exercise program while
taking JARDIANCE.

When taking JARDIANCE, you may have sugar in your urine,
which will show up on a urine test.

What are the possible side effects of JARDIANCE?

JARDIANCE may cause serious side effects, including:

See "What is the most important information I should
know about JARDIANCE?"

Ketoacidosis (increased ketones in your blood or urine).Ketoacidosis has happened in people who have type 1 diabetes or type 2
diabetes, during treatment with JARDIANCE. Ketoacidosis is a serious condition,
which may need to be treated in a hospital. Ketoacidosis may lead to death. Ketoacidosis
can happen with JARDIANCE even if your blood sugar is less than 250 mg/dL. Stop
taking JARDIANCE and call your doctor right away if you get any of the
following symptoms:

If you get any of these symptoms during treatment with
JARDIANCE, if possible, check for ketones in your urine, even if your blood
sugar is less than 250 mg/dL.

Serious urinary tract infections. Serious urinary
tract infections that may lead to hospitalization have happened in people who
are taking JARDIANCE. Tell your doctor if you have any signs or symptoms of a
urinary tract infection such as a burning feeling when passing urine, a need to
urinate often, the need to urinate right away, pain in the lower part of your
stomach (pelvis), or blood in the urine. Sometimes people also may have a
fever, back pain, nausea or vomiting.

Low blood sugar (hypoglycemia). If you take
JARDIANCE with another medicine that can cause low blood sugar, such as a
sulfonylurea or insulin, your risk of getting low blood sugar is higher. The
dose of your sulfonylurea medicine or insulin may need to be lowered while you
take JARDIANCE. Signs and symptoms of low blood sugar may include:

Kidney problems. Sudden kidney injury has happened
to people taking JARDIANCE. Talk to your doctor right away if you:

reduce the amount of food or liquid you drink for
example, if you are sick or cannot eat or

you start to lose liquids from your body for example,
from vomiting, diarrhea or being in the sun too long

Increased fats in your blood (cholesterol)

These are not all the possible side effects of JARDIANCE.
For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088.

How should I store JARDIANCE?

Store JARDIANCE at room temperature 68°F to
77°F (20°C to 25°C).

General information about the safe and effective use
of JARDIANCE.

Medicines are sometimes prescribed for purposes other
than those listed in Patient Information. Do not use JARDIANCE for a condition
for which it is not prescribed. Do not give JARDIANCE to other people, even if
they have the same symptoms you have. It may harm them.

This Patient Information summarizes the most important
information about JARDIANCE. If you would like more information, talk with your
doctor. You can ask your pharmacist or doctor for information about JARDIANCE
that is written for health professionals.

For more information about JARDIANCE, go to
www.jardiance.com, scan the code below, or call Boehringer Ingelheim
Pharmaceuticals, Inc. at 1-800-542-6257 or (TTY) 1-800-459-9906.